Thenylamines



- dimines. capable of participating in the Mannich reacpronounced reactivity.

Patented Oct. 31, 1950 Howard D. Hartough, Pitman, and Emil Koft, r.,

Woodbury Heights, N. J., assignors to Socony- Vacuum Oil Company, Incorporated, a corporation of New York. 1

No Drawing. Application April 21, 1948, Serial No. 22,495

. 9 Claims.

' The present invention is related to the preparation of N-methyl amines from formaldimines and, more particularly, to the preparation of N- methyl thenylamines from thenylformaldimine.

v In application for United States Letters 'Patent Serial No. 782,962 filed October 29, 1947 in the name ofI-Ioward D. Hartough the prepara- "tionof formaldimines was disclosed. Therein it was established that the formaldimines of substances capable of participating in the Mannich reaction can be prepared in a manner analogous to that employed in preparing the thenylformal- F. F. Blicke has defined the compounds tion as having at least one hydrogen atom of It has now been found that when these formaldimines are reduced N-methylamines are formed in accordance with :the following equation where R is the residue of 1a thiophene compound:

formaldimine N-methyl thenylamine The reduction can be carried out in any suitable manner, for example, by hydrogen produced by the reaction of zinc and hydrochloric acid or by hydrogen in the presence of a suitable catalyst.

"When the reduction is carried out in the'pres- I e'nceofforinaldehyde the N,N-dimethylamine is obtainedin accordance with the following equations: fore) 3 p (R has thesame significance {as hereton I R-c112N=oH2 2H Roma ce;

CH3 N,N-dimethylamine Thiophene and alkyl thiophenes also arecapable of entering intoa reaction to form a com- ;pound having a structure corresponding to the j pheneradical having two "unsubstituted alpha 2 positions) which likewise may be reduced in a similar manner to yield the di-(N,N-.dimethylaminomethyl) derivative of the starting compound in accordance with the following equations:

Thus, in general, the present invention provides for the reduction of thenylformaldimines been prepared.

either after separation from the reaction mixture in which the formaldimines have been prepared or, particularly when prepared in accordance with the method disclosed in copending application Serial No.'782,962, without separation from the reaction in which the formaldimines have In the latter method particular advantage is taken of the fact that while the thenylformaldimines are relatively unstable, the reduction products are stable. For ease of des'cription and illustration the preparation of the reduction products of the 2-thenylfo-rmaldimine will be described.

The preparation N-me'thyl-2-thenylamine can becarried outin a relatively eas 'manner. The

N (2-thenyl)formaldimine is prepared as described in copending application Serial No.

182,962 by mixing ammonium halide, aqueous formaldehyde and thiophene, heating the mixture to a temperature not exceeding 70 .C. to initiate reaction, reducing the temperature to ambient temperatures, e. g., 10 to 20 C. separatim; an aqueous layer, neutralizing the aqueous layer and recovering the N-(Z-thenyDformaldimine set free by the neutralization.

Example I "The formaldimine so prepared is then reduced 'in Example I.

as follows; about 50 parts by weight of N-(2- thenyDformaldimine (0.4 mole), about 200 parts by weight of water and about 40 parts by weight of zinc dust are mixed and warmed to about 45 C. while stirring vigorously. To the well-stirred lution. The reaction mixture was stirred vigorously until the temperature had dropped below 50 C. at which time about 200 parts by weight of zinc dust were added slowly while maintaining the 5 temperature within the range 40 to 45 C. To and warmed mixture about 132 parts by weight this mixture were added slowly a mixture of about of concentrated hydrochloric acid, 1. e., and ex 305 parts by weight of concentrated hydrochlocess, diluted with about 150 parts by weight of ride acid in about 300 parts by weight of water. water were added gradual y- After the a d The mixture was stirred for about two hours at of the hydrochloric acid the temperature of the to C, and then warmed to 55 to 60 C. and mixture was maintained in the range 83 to 102 held in that range for an additional three hours. C. for about seven hours, i. e., until substantially Unreacted zinc was removed and the reaction all of the zinc dissolved. The reaction mixture mixture neutralized with aqueous 30 per cent sowas cooled to room temperature, neutralized with diu hydroxide solution. Th inc hydroxide was aqueous 40 per cent sodium hydroxide and the 15 separated, washed and digested with benzene. zinc hydroxide filtered oif. The filter was washed The aqueous solution of the neutralized reaction with benzene and the filtrate was extracted With mixture was extracted ith benzene, The benbenze-ne and the benzene extracts combined. zene solutions were combined, dried and the ben- The benzene was distilled from the extr ct zene removed. The residue was distilled under The residue from the benzene extracts was dis- 20 reduced pressure into fractions as indicated heretilled to yield the following fractions: inafter.

e?" mares. time: 55 Basra tast stats? Residue 30 The phenylthiourea of fraction number 1 was prepared in the conventional manner and had a melting point of 127 to 128 C. A mixed melting point with an authentic sample of N-(2-thenyl) N-methyl-N'-phenylthiourea gave no depression establishing that fraction number 1 was N-methyl-2-theny1amine. Fraction number 3 was predominantly unreacted N- 2-thenyl) formaldimine.

Example II N,N-dimethyl-2-thenylamine was prepared by reducing about 50 parts by weight of N-(Z-thenyDfOrmaldimine in the presence of about 33 parts by weight of aqueous 36 per cent formaldehyde solution (about 0.4 mole) with about 40 parts by weight of zinc dust, 132 parts by weight of concentrated hydrochloric acid and about 350 parts by weight of water in the manner described Distillation of the benzene extracts yield a product having a boiling point of to 61 C. at a pressure of 10 millimeters of mercury and a refractive index of n 1.5188. A crystalline methiodide of this compound was prepared and melted at 152.5 to 153 C. A methiodide of an authentic sample of N,N-dimethy1-2-thenylamine was prepared. The N,N-dimethyl-2-theninbefore was determined.

Example III About 168 parts by weight of thiophene (about 2 moles) and about 108 parts by weight of ammonium chloride (about 2 moles) were mixed. To the mixture so formed about 1'70 parts by weight of aqueou 36 per cent formaldehyde solution 5 (about 2 moles) were added. The resultant mixture Was warmed to about 65 C. and held at that temperature while adding an additional 170 parts I by weight of aqueous 36 per cent formaldehyde so- A methiodide was prepared from fraction number 1 in a conventional procedure. When recrystallized from ethanol the methiodide of fraction number 1 melted at 151.5 to 152 C.

CsHnINS I Nitrogen Sulfur Calculated. 4. 95 ll. 32 Found 4. 95 11. 12

A mixture of this methiodide with an authentic sample of the methiodide of N,N-dimethyl-2- thenylamine melted without depression of the melting point of the authentic methiodide. Consequently, the primary constituent of fraction numberlis Example IV Temp., Pressure Parts by Refractive Fraction C. mm. of Hg Weight Index no 64 10 66 10 31 1. 5183 115 10 3 1. 5287 1 144 10 11 1. 5453 144+ 10 4 1. 5607 Residue 5 1- 1 Main boiling range 134 to 144.

Fraction number 1 was essentially all N,N-dimethyl-Z-thenylamine. A methiodide was prepared from fraction number 3 by reaction with methyl iodide in a conventional manner. The

crystalline 'dimethiodide derivative after recrystallization from ethanol melted at 241 to;243 C.

i im'corrc'cted) .with decomposition. Thenformula C12H24I2NZS was established from the analysis.

Cl2H24I 2N2S Nitrogen Sulfur Carbon? iii-Ty drogen Calculated 5. 81 6. 65 29. 93 5. 02 Found 5. 84 6. 89 29. 87

It follows that the essential constituent of fraction number 3 is di-2,5-(N,N-dimethyl aminomethyDthiophene corresponding to the formula H30 H I H /GHa N l S s. HaC III H CHa In a similar manner the corresponding derivatives of methyl thiophene and other alkyl thiophenes can be prepared. Thus, for example, 2-methylthiophene when reacted with ammonium halide and formaldehyde as described hereinbefore and the N-(5-methyl-2-thenyD- formaldimine reduced either with zinc dustand hydrochloric acid or hydrogen in the presence of v tion catalysts which retain their activity in the presence of sulfur yields N,N-dimethyl5-methyl-2-thenylamine. The formaldehyde may be present as unreacted formaldehyde when the formaldimine is not separated from the reaction mixture in which the formaldimine is obtained or may be formaldehyde which is added to the separated, substantially pure formaldimine. In general, the alkylthiophenes having the alkyl substituent in the 2- or 5-positions yield only the N,N-dimethyl derivatives. However, the alkyl thiophenes having the alkyl substituents in the 3 and/or 4 positions yield not only the N,N-dimethyl derivatives but also the alkyl derivatives of di 2,5 (N,N-dimethyl aminomethyDthiophene. Consequently, in general the thenylamines and di-2,5-(N,N-dimethyl aminomethyl) thiophenes corresponding to the formulae given hereinafter can be obtained:

R-R n n i R C-N H CH3 where R is hydrogen, an alkyl group, or a halogen and We claim:

1. Di 2,5 (N,N-dimethyl aminomethyl)thiophene.

' 2". Amino'ethylthlophenes hayinga composition corresponding to the formula R' "in" Q in which R is' selected from the group consistwing rof hydrogen, (an alkyl group, a halogen,

where R, R" and R' are alkyl groups, halogens and hydrogens and at least one of R, R" and R'" is an alkyl group or a hydrogen.

6. Derivatives of 2,5-di-(N,N-dimethyl) aminomethyl thiophene, corresponding to the formula where R and R" are alkyl groups, halogens and hydrogens and at least one of R and R is an alkyl group or a hydrogen.

7. A method for preparing hydrogenation products from N-2-thenylformaldimine, which comprises mixing thiophene and ammonium halide with an amount of formaldehyde in excess of one mole of formaldehyde, per mole of thiophene, to form a reaction mixture, heating said reaction mixture to about 65 C., cooling said reaction mixture to about ill-50 0., adding an amount of metallic zinc equal to at least 50% by weight of the thiophene, ammonium halide andformaldehyde whilst maintaining the reaction temperature within the range of about 40- 45" C., adding sufficient dilute mineral acid to said reaction mixture to react with said zinc, warming said reaction mixture to about 55-60 0., maintaining said reaction mixture at about 55-60 C. until substantially all of. said zinc is dissolved, neutralizing said reaction mixture, extracting said reaction mixture with benzene, and

recovering hydrogenation products of said theynl formaldimine.

' (8. A method for preparing alpha aminomethylthiophene, N-methyland (N,N'-dimethyl)-alpha-aminomethylthiophenes, which comprises.

hydrogenating N- (Z-thenyDfOrmaIdimine in the presence of formaldehyde at a temperature of about 55-60 C.

9. A method for preparing di-(N,N-dimethyDaminomethylthiophene, which comprises hydrogenating a compound having a composition corresponding to the formula in the presence of formaldehyde at a temperature of about 55-60 C., R being a thiophene radical having two unsubstituted alpha positions R UNITED STATES PATENTS and R" being substituents in the beta positions Number Name Date T" of R selected from the group consisting of hydro- 2,500,822 Hartough Mar. 4 1950 gen, halogen and alkyl. 7

HOWARD D. HARTOUGH. 5 OTHER REFERENCES EMIL KOFT. JR. Hartough, J. Am. Chem. Soc. '70, 1146-1149,

. ,REFERENCES CITED The following references are of record in the fi jle of this' patent:

Certificate of Correction Patent No. 2,528,306 October 31, 1950 HOWARD D. HARTOUGH ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requlring correction as follows:

Column 1, lines 34 to 36, for that portion of the formula reading RCHgIk-CH. read ROHslh-C H:

and that the said Letters Patent should be read as corrected above, so that the same may conform to the record of the case in the Patent Oflice.

Signed and sealed this 1st day of May, A. D. 1951.

THOMAS F. MURPHY,

Assistant Oommissz'oner of Patents. 

2. AMINOETHYLTHIOPHENES HAVING A COMPOSITION CORRESPONDING TO THE FORMULA 